A multicentre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of oral dosing with GW679769 (50 mg or 150 mg) for 3 consecutive days in conjunction with a single intravenous dose of ondansetron for the prevention of post-operative and post-discharge nausea and vomiting in at risk females undergoing laparoscopic/laparotomic surgical procedures.
- Conditions
- Post Operative Nausea and Vomiting (PONV)Post Discharge Nausea and Vomiting (PDNV)
- Registration Number
- EUCTR2004-000369-37-HU
- Lead Sponsor
- GlaxoSmithKline Group of Companies
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 411
1. Female with the following three risk factors:
• Pre-menopausal or peri-menopausal between the ages of 18 – 55 years, who is not of childbearing potential (i.e., physically incapable of becoming pregnant) or who demonstrates a negative serum or a negative urine pregnancy test within 24 hours prior to the first administration of the investigational product and agrees to:
abstain from sexual intercourse for 2 weeks prior to administration of the first dose of the investigational product until 30 days after the final dose of the investigational product, or
use hormonal methods of birth control (e.g., oral, injectable, or implantable) or other highly effective method of contraception [e.g., an intrauterine device (IUD)] in conjunction with a barrier method of contraception (condom, spermicidal foam, sponge, gel, diaphragm) if engaging in sexual intercourse for at least seven days prior to the first dose of the investigational product and continuing until 30 days after the final dose of the investigational product.
• Has never smoked or used (e.g., chewing) tobacco (including nicotine patches or other nicotine-withdrawal formulations) for the previous 12 months.
• Known to have a history of post-operative nausea and vomiting and/or motion sickness.
2. Is undergoing a laparoscopic/laparotomic gynecological surgical procedure or laparoscopic cholecystectomy that is scheduled for no less than 1 hour and no longer than 3 hours in duration. For the purposes of this study, scheduled” is considered the duration of time that the surgical suite is blocked for the procedure (i.e., the operating room block time) or the duration of time in which it is anticipated that the subject will be in the operative preparation/operating room.
3. Is scheduled to receive general inhalational anesthesia with an anesthetic regimen as described in the Anesthetic Regimen (see Section 4.2 Anesthetic and Analgesic Regimens”).
4. Meets the American Society of Anesthesiologists (ASA) Physical Status Classification (see Section 14.3.) of I or II preoperatively on the day of surgery.
5. Has hematology and blood chemistry values within acceptable limits (i.e., within 10% outside (either above or below) normal reference values, unless otherwise specified) for surgery, including, but not limited to:
• Hemoglobin, hematocrit, total white blood cell count, platelet counts.
• Alkaline phosphatase, blood urea nitrogen or serum urea, electrolytes (sodium, potassium, chloride, bicarbonate).
• Liver function tests (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <1.5 times the upper limit of normal), serum creatinine (<1.5 times the upper limit of normal), total bilirubin (<1.5 times the upper limit of normal).
Note, subjects still may be eligible if values do not fall within these extended reference ranges and the Investigator considers the values to result from the underlying medical condition being treated by the scheduled surgery (e.g., bleeding fibroids, cholecystitis) and/or a concomitant medication administered to treat the underlying medical condition. Individual cases must be discussed with the local GlaxoSmithKline Medical Department for approval prior to administration of the GW679769 investigational product on Study Day 1.
6. Is able and willing to complete daily components of the subject diary preoperatively on the day of surgery and until the end of the 120-hour assessment period, and will be available to answer follow-up questions via telepho
1.Meets ASA Physical Status Classification of III, IV, or V preoperatively on the day of surgery.
2.Is pregnant or lactating.
3.Is post-menopausal. If the last menstrual period was within the previous 18 months, a follicle stimulating hormone (FSH) evaluation in the postmenopausal range will satisfy that the subject is post-menopausal.
4.Is scheduled to undergo only a laparoscopic biopsy.
5.Is scheduled to receive neuroaxial anesthesia (e.g., epidural, spinal, or caudal anesthesia) or total IV anesthesia.
6.Is scheduled to receive propofol for maintenance of anesthesia.
7.Is expected to have gastric contents suctioned throughout the surgical procedure via a nasogastric tube, or a nasogastric or oral gastric tube during the post-operative period. A single pass at the end of the surgical procedure and intraoperative gastric suctioning of air are permitted.
8.Has been taking more than 10 – 15 mg of oxycodone, or an equivalent opioid dose, on a regular, daily basis, for more than three consecutive days in the week prior to surgery.
9.Has received an investigational drug in the previous 30 days or who is scheduled to receive any investigational drug in addition to GW679769 during the study period.
10.Has persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to, gastric outlet obstruction, hypercalcemia, active peptic ulcer, increased intracranial pressure, or brain metastases.
11.Has experienced retching or vomiting or uncontrolled nausea within 48 hours prior to administration of the investigational product.
12.Has experienced significant nausea (e.g., ? 25 mm on a visual analogue scale (VAS)) in the 24-hour period prior to receiving the investigational product.
13.Has received radiation therapy to the abdomen or the pelvis in the seven days prior to receiving the investigational product and/or will receive radiation therapy to the abdomen or the pelvis during the evaluation period.
14.Has a history of wound dehiscence.
15.Has a history of any other illness, which, in the opinion of the Investigator, may pose an unacceptable risk by administration of the investigational product.
16.Has any current or past medical condition (e.g., vagotomy) and/or require medication to treat a condition that could confound the evaluation of the data collected in this clinical trial.
17.Has a known hypersensitivity or contraindication to ondansetron hydrochloride or ondansetron, another 5-HT3 receptor antagonist, any scheduled anesthetic or analgesic agents, or any component of GW679769.
18.Has a known hypersensitivity to fentanyl and/or ketorolac tromethamine.
19.Has a known allergy to eggs or egg products.
20.Is scheduled to receive antiemetics not outlined in the study dosing scheme.
21.Has received medication with known or potential antiemetic activity within the 24 hour period prior to receiving the investigational product. This includes, but is not limited to:
•5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonosetron is not permitted for seven days prior to the study.
•Benzamide/benzamide derivatives (e.g., metoclopramide, alizapride).
•Benzodiazepines (except if the subject is receiving such medication for sleep and has been on a stable dose for at least seven days prior to the first dose of investigational product; however, lorazepam is prohibited).
•Phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method